What are the recommended doses of weak and strong opioids, such as codeine (opioid analgesic) and morphine (opioid analgesic), for pain management?

Recommended Doses of Weak and Strong Opioids for Pain Management

For weak opioids treating mild to moderate pain, codeine 30-60 mg every 4-6 hours (maximum 240 mg/day) and tramadol 50-100 mg every 4-6 hours (maximum 400 mg/day) are standard doses, while for strong opioids treating moderate to severe pain, oral morphine should start at 5-15 mg immediate-release every 4 hours or 20-40 mg daily for opioid-naïve patients, with no upper dose limit. 1, 2

Weak Opioids (WHO Level II)

Codeine

• Starting dose: 30-60 mg orally every 4-6 hours 1, 3
• Maximum daily dose: 240 mg/day 1
• Relative potency: Approximately 0.1-0.15 times oral morphine 1
• Critical caution: Codeine requires CYP2D6 metabolism to convert to morphine for analgesic effect; 7-10% of Caucasian patients are poor metabolizers who receive minimal analgesia but still experience side effects 4, 5
• Constipation prophylaxis must always be prescribed 1

Tramadol

• Starting dose: 50-100 mg orally every 4-6 hours 1
• Maximum daily dose: 400 mg/day 1
• Modified-release formulation: 100-200 mg every 12 hours 1
• Relative potency: 0.1-0.2 times oral morphine 1
• Contraindications: Do not combine with monoamine oxidase inhibitors 1
• Use with extreme caution in patients with epilepsy risk or when combined with antidepressants 1, 6

Dihydrocodeine

• Starting dose: 60-120 mg modified-release tablets 1
• Maximum daily dose: 240 mg/day 1
• Duration of action: 12 hours for modified-release formulation 1
• Relative potency: 0.17 times oral morphine 1

Strong Opioids (WHO Level III)

Morphine (First-Line Choice)

Morphine is the gold standard first-line strong opioid for moderate to severe cancer pain. 1, 2

Oral Administration

• Starting dose for opioid-naïve patients: 20-40 mg daily of sustained-release formulation OR 5-15 mg immediate-release every 4 hours 1, 2
• No maximum daily dose - titrate to effect 1
• Oral to parenteral conversion ratio: 1:2 to 1:3 (oral morphine is 2-3 times less potent than IV/subcutaneous) 1

Parenteral Administration

• Starting IV/subcutaneous dose: 2-5 mg for urgent pain relief 2
• Standard IV dose: 5-10 mg 1
• Relative potency: Parenteral morphine is 3 times more potent than oral 1

Alternative Strong Opioids

Oxycodone

• Starting dose: 20 mg orally 1
• Relative potency: 2 times oral morphine 1
• No maximum daily dose 1

Hydromorphone

• Starting dose: 8 mg orally 1
• Relative potency: 7.5 times oral morphine 1
• Parenteral dose: 0.015 mg/kg IV with quicker onset than morphine 6
• No maximum daily dose 1

Fentanyl (Transdermal)

• Starting dose: 12 mcg/hour patch (equivalent to 30-60 mg oral morphine daily) 1
• Relative potency: 4 times oral morphine when comparing daily doses 1
• Preferred in chronic kidney disease stages 4-5 (GFR <30 mL/min) 1, 6

Buprenorphine

• Oral starting dose: 0.4 mg 1
• IV dose: 0.3-0.6 mg 1
• Transdermal starting dose: 17.5-35 mcg/hour 1
• Maximum oral daily dose: 4 mg 1
• Preferred in chronic kidney disease stages 4-5 1, 6

Breakthrough Pain Dosing

The breakthrough dose should be 10% of the total daily opioid dose, administered as immediate-release formulation. 1

• If more than 4 breakthrough doses per day are required, increase the baseline sustained-release opioid dose 1
• Breakthrough doses can be given up to hourly during titration 1
• Adjust regular sustained-release dose based on total rescue medication used in 24 hours 1

Critical Dosing Principles

Route of Administration

• Oral route is first choice when possible 1, 6, 7
• Subcutaneous route is the preferred alternative when oral route is unavailable - simple and effective for morphine, diamorphine, and hydromorphone 1
• IV route is indicated for rapid titration, peripheral edema, coagulation disorders, or need for high volumes 1

Scheduling

• Prescribe analgesics around-the-clock (ATC), not "as needed" for chronic pain 1, 7
• Immediate-release formulations every 4 hours plus rescue doses for breakthrough pain 1
• Sustained-release formulations every 12 hours plus immediate-release rescue doses 1

Titration Strategy

• Start at the lowest effective dose 2, 3
• For most patients, optimal dose is well below 200 mg morphine equivalent daily 3
• Optimal dose improves function or decreases pain by at least 30% 3

Common Pitfalls and Critical Cautions

Renal Impairment

• Avoid morphine, hydromorphone, and codeine in chronic kidney disease stages 4-5 due to accumulation of neurotoxic metabolites 1, 2, 6
• Use fentanyl or buprenorphine instead in severe renal impairment 1, 6

Weak Opioids Are Not Necessarily Safer

Do not assume weak opioids like codeine or tramadol are safer than low-dose morphine - they carry similar addiction and respiratory depression risks with more unpredictable efficacy. 2, 4

• Low-dose morphine has higher response rates and earlier pain relief onset compared to codeine and tramadol 2
• Weak opioids require at least as much vigilance as morphine despite regulatory differences 4

Constipation Management

• Always prescribe prophylactic laxatives when initiating any opioid therapy 1, 2, 6
• Constipation should be anticipated with all opioids, especially codeine 1

Discontinuation

• Never stop opioids abruptly 2, 6
• Taper by 30-50% over approximately one week if discontinuation is needed 2, 6

Drug Interactions

• Tramadol: contraindicated with MAO inhibitors 1, 6
• Dextropropoxyphene: do not combine with carbamazepine (increases carbamazepine levels) 1
• Codeine and tramadol efficacy varies widely based on CYP2D6 genotype 4, 5